Feline Ehrlichiosis and Hemobartonellosis
Michael Lappin United States
Cats experimentally infected with E. risticii develop morulae in mononuclear cells and occasionally develop clinical signs of disease including fever, depression, lymphadenopathy, anorexia, and diarrhea. Cats experimentally infected with E. equi develop morulae in neutrophils and eosinophils, not mononuclear cells.
Ehrlichia canis DNA and DNA genetically identical to the granulocytic Ehrlichia of horses, dogs, and humans in Sweden have been amplified from naturally exposed cats. Ehrlichia-like morula have been detected in mononuclear cells or neutrophils of naturally-exposed cats in the United States, Kenya, Brazil, France, Sweden, and Thailand. Clinical diagnosis has been also been based on the combination of either positive E. canis or E. risticii serology, clinical or laboratory findings consistent with ehrlichial infection, exclusion of other causes, and response to an anti-rickettsial drug. There are currently over 50 cases of suspected or proven cases of feline ehrlichiosis in the world’s literature. It is unknown how the clinically ill, naturally exposed cats described in the literature were infected. Exposure to arthropods has been reported in about 30% of the cases. Pathogenesis of disease associated with ehrlichiosis in cats is unknown.
Of the cats in which age was reported, most were older than two years. Most cats were domestic shorthaired and both males and females have been affected. Anorexia, fever, inappetence, lethargy, weight loss, hyperesthesia or joint pain, pale mucous membranes, splenomegaly, dyspnea, and lymphadenomegaly were the most common historical and physical examination abnormalities. Concurrent diseases are rarely reported but included Hemobartorella felis infection and lymphosarcoma.
Anemia is a common laboratory abnormality and is usually non-regenerative. Leukopenia, leukocytosis characterized by neutrophilia, lymphocytosis, monocytosis, and intermittent thrombocytopenia were reported for some cats. Hyperglobulinemia was reported for 11 cats; protein electrophoresis documented polyclonal gammopathy in the cat assayed. However, an epidemiological link has been made between presence of Ehrlichia spp. antibodies in serum and monoclonal gammopathy.
Some cats with suspected clinical ehrlichiosis had antibodies against E. canis and E. risticii and some had antibodies against E. risticii alone or E. canis alone. Western blot immunoassay has been used to confirm some E. risticii positive results. Positive serologic test results occur in healthy cats as well as clinically ill cats and so a diagnosis of clinical ehrlichiosis should not be based on serologic test results alone. A tentative diagnosis of feline clinical ehrlichiosis can be based on the combination of positive serologic test results, clinical signs of disease consistent with Ehrlichia infection, exclusion of other causes of the disease syndrome, and response to anti-rickettsial drugs. Ehrlichia spp. has been cultured from some cats on monocyte cell cultures. Polymerase chain reaction and gene sequencing can also be used to confirm infection.
Clinical improvement after therapy with tetracycline, doxycycline, or imidocarb dipropionate was reported for most cats. However, for some cats a positive response to therapy was a criterion for the diagnosis of ehrlichiosis.
There are currently no known direct public health risks associated Ehrlichia spp. infected cats. However, since some species of Ehrlichia cross-infect, it is possible that cats could be a reservoir for species that infect people. The granulocytic strain documented in cats was identical genetically to the granulocytic strain that infects people. Thus, it seems prudent to recommend arthropod control for cats.
Haemobartonella felis is a gram-negative, epicellular parasite of feline erythrocytes. The organism was classified in the family Anaplasmataceae but recently was shown to be more closely related to the mycoplasma. Haemobartonella felis is species-specific and cannot survive outside the host. To date, attempts to culture the organism have failed. However, based on morphologic and genetic characterization there are at least two variants. The small variant of the organism has been designated the California strain (Hfsm) and the large form has been designated the Ohio strain (Hflg). Coinfected, naturally exposed cats have been detected but information concerning coinfection in experimentally inoculated cats is currently lacking.
Haemobartonella felis has been transmitted experimentally by IV, IP, and oral inoculation of blood. It appears likely that blood sucking arthropods like fleas and ticks can transmit the disease. Clinically ill queens can infect kittens; whether transmission occurs in utero, during parturition, or from nursing has not been determined. Transmission by biting has been hypothesized. Red blood cell destruction is due primarily to immune-mediated events; direct injury to red blood cells induced by the organism is minimal. The attachment of the organism to erythrocytes commonly leads to the development of antibodies against the organism as well as to erythrocyte antigens. Positive Coomb's tests are common. Most infected erythrocytes are removed by the reticuloendothelial system in the liver, lungs, spleen, and bone marrow. Some infected erythrocytes have the organism stripped from the surface in the spleen by pitting which leads to a shortened erythrocyte lifespan. In at least two studies of experimentally infected cats, the Hflg strain was apparently more pathogenic than the Hfsm strain; all Hflg inoculated cats became clinical ill whereas Hfsm inoculated cats were subclinically infected.
In naturally exposed cats, clinical disease occurs in immunocompetent or immunosuppressed cats. Clinical signs of disease depend on the degree of anemia, the stage of infection, and the immune status of infected cats. Clinical signs and physical examination abnormalities associated with anemia are most common and include pale mucous membranes, depression, inappetence, weakness, and occasionally, icterus and splenomegaly. Fever occurs in some acutely infected cats and may be intermittent in chronically infected cats. Evidence of coexisting disease may be present. Weight loss is common in chronically infected cats. Cats in the chronic phase can be subclinically infected only to have recurrence of clinical disease following periods of stress. In cats experimentally inoculated with the Hflg strain, significant clinical signs were consistent with developing anemia and were most apparent approximately three weeks post-inoculation.
The anemia associated with haemobartonellosis is generally macrocytic, normochromic but may be macrocytic, hypochromic if coinfections leading to chronic inflammation exist. Chronic non-regenerative anemia is unusual in haemobartonellosis. Neutrophilia and monocytosis have been reported in some H. felis infected cats. Diagnosis is based on demonstration of the organism on the surface of erythrocytes on examination of a thin blood film or polymerase chain reaction (PCR). Organism numbers fluctuate and so blood film examination can be falsely negative up to 50% of the time. The organism may be difficult to find cytologically, particularly in the chronic phase. Thus, the PCR is the test of choice due to sensitivity. Primers are available that detect a segment of the 16S rRNA gene common to both sequenced strains of H. felis.
Since haemobartonellosis and primary immune hemolytic anemia are difficult to differentiate, cats with severe, regenerative hemolytic anemia should be treated with glucocorticoids and antibiotics. Historically, oxytetracycline was commonly recommended at 22 mg/kg q8h PO. Doxycycline has fewer side effects than other tetracyclines in cats and so is probably preferred. Doxycycline should be given at 5–10 mg/kg q12-24h PO for 14–21 days. If autoagglutination is evident, prednisolone is usually prescribed at 1 mg/kg q12h PO for the first seven days or until autoagglutination is no longer evident. Tetracyclines utilized to date appear to lessen parasitemia and clinical signs of disease but probably do not clear the organism from the body. Experimentally infected cats treated with doxycycline have apparent clinical response (Foley JE et al., 1998; Berent LM et al., 1998) but the organism could still be detected by PCR when the cats were given methylprednisolone acetate (Berent LM et al., 1998). In cats intolerant of tetracyclines, quinolones should be considered. Efficacy of quinolones is for the most part, unknown. However, enrofloxacin given at 5 mg/kg q24h PO is tolerated by cats and may be effective for control of clinical signs based on limited clinical experiences. Blood transfusion should be given if clinically indicated.
The prognosis is generally good for immunocompetent cats. Potential arthropod vectors should be controlled. Cats should be housed indoors to avoid vectors and fighting. Clinic blood donor cats should be screened for H. felis infection by polymerase chain reaction.
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